Background-Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor.

Context and objective: Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein. Subjects and methods:One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): !25 kg/m 2 ) and 89 obese (overweight/obese; BMI: R25!40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects. Results: There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (bZ0.29, PZ0.08; R 2 Z0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (bZ0.59, P!0.0001; R 2 Z0.40). Conclusions: In our population, RBP4 circulating levels were not significantly correlated with obesityrelated parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.

Obesity is linked to a low-level chronic inflammatory state that may contribute to the development of associated metabolic complications. Retinol-binding protein 4 (RBP4) is an adipokine associated with parameters of obesity including insulin resistance indices, body mass index, waist circumference, lipid profile, and recently, with circulating inflammatory factors. Due to the infiltration of adipose tissue in obesity by macrophages derived from circulating monocytes and, on the other hand, the existence of a close genetic relationship between adipocytes and macrophages, we decided to examine if RBP4 is expressed in monocytes and/or primary human macrophages. While we did not detect expression of RBP4 in undifferentiated monocytes, RBP4 expression became evident during the differentiation of monocytes into macrophages and was highest in differentiated macrophages. Once we demonstrated the expression of RBP4 in macrophages, we checked if RBP4 expression could be regulated by inflammatory stimuli such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or the endotoxin lipopolysaccharide (LPS). We observed that while RBP4 expression was strongly inhibited by TNF-α and LPS, it was not affected by IL-6. Our results highlight the complexity behind the regulation of this adipokine and demonstrate that RBP4 expression in macrophages could be modulated by inflammatory stimuli.

No abstract

No abstract